High protein liquid enteral nutritional composition

ABSTRACT

The present invention relates in general to a shelf-stable liquid enteral composition for providing nutrition, either as a supplement, or as a complete nutrition, with a high protein content of a non-hydrolysed globular protein, in particular a whey protein.

FIELD OF THE INVENTION

This invention is concerned with a method for the heat-treatment of anon-hydrolysed globular protein, the non-hydrolysed heat-treatedglobular protein per se, a shelf-stable liquid enteral nutritionalcomposition with a high content of non-hydrolysed globular protein as amajor protein source, processes for the preparation thereof and use ofsaid liquid enteral nutritional composition for the treatment of personsin need thereof.

BACKGROUND OF THE INVENTION Clinical Problem

Some patients need nutrition, either as a supplement, or as a completenutrition, in the smallest volume of liquid.

These patients can be cachectic patients or persons suffering fromend-stage AIDS, cancer or cancer treatment, severe pulmonary diseaseslike COPD (chronic obstructive pulmonary disease), tuberculosis andother infection diseases or persons that experienced severe surgery ortrauma like burns. Furthermore, persons suffering from disorders in thethroat or mouth such as oesophageal cancer or stomatitis and personshaving problems with swallowing like dysphagic persons, require specialliquid, low-volume nutrition. Also, persons just suffering from reducedappetite or loss of taste, will benefit from low-volume, preferablyliquid, food.

These patients can also be elderly persons, in particular frail elderlyand elderly at risk of becoming frail. In this regard, although anelderly person's energy needs may be reduced, their ability to consumeproducts may also be diminished. For example, they may have difficultyconsuming a product due to, e.g., swallowing difficulties, or due thetoo large amount of product they need to consume to meet the dailyintake of nutrients. Hence, compliance is not optimal, and often, theintake is suboptimal, leading to suboptimal nourishment, and in the end,to malnutrition.

In this respect, it is submitted that in the context of thisapplication, an elderly person is a person of the age of 50 or more, inparticular of the age of 55 or more, more in particular of the age of 60or more, more in particular of the age of 65 or more. This rather broaddefinition takes into account the fact that the average age variesbetween different populations, on different continents, etc. Mostdeveloped world countries have accepted the chronological age of 65years as a definition of ‘elderly’ or older person (associated with theage at which one may begin to receive pension benefits), but like manywesternized concepts, this does not adapt well to e.g. the situation inAfrica. At the moment, there is no United Nations (UN) standardnumerical criterion, but the UN agreed cut-off is 60+ years to refer tothe older population in Western world. The more traditional Africandefinitions of an elder or ‘elderly’ person correlate with thechronological ages of 50 to 65 years, depending on the setting, theregion and the country.

The aforementioned groups of patients may be extremely sensitive to foodconsistency and to the organoleptic properties of the product such as,for instance viscosity, mouth feel, taste, smell and colour. Also,patients such as cachectic patients, typically suffer from extremeweakness which often prevents them from sitting in a vertical positionand from their ability to drink the food from a carton or even to suckit from a straw. These patients benefit well from liquid low-volumeenteral compositions with a high content of nutrients.

Therefore, the problem underlying the present invention is to provide ashelf-stable liquid enteral composition for providing nutrition, eitheras a supplement, or as a complete nutrition, with a high content ofnon-hydrolysed globular protein as major protein source, in particularwhey proteins, in the smallest volume of liquid, and which supportsnutrition and well-being in the different patient groups mentionedabove.

In the context of the current application, enteral means any form ofadministration that involves any part of the gastrointestinal tract,i.e. by mouth (orally), by gastric feeding tube, duodenal feeding tube,or gastrostomy, and rectally.

TECHNICAL PROBLEM

Major technical difficulties exists in producing such a shelf-stableliquid enteral nutritional composition with a high content ofnon-hydrolysed globular proteins, in particular non-hydrolysed wheyproteins.

For example, increasing the amount of proteins leads to precipitationand sedimentation of proteins and other ingredients, such as lipids andcarbohydrates, which imparts nutrient intake.

Concentrating liquids also increases the chance of undesiredinteractions between ingredients which reduces stability, especiallyduring heating and long-term storage.

Furthermore, increasing the protein content in a nutritional liquidcomposition may increase the overall viscosity of the composition. Thiscan make the liquid nutritional composition difficult to consume oradminister, and can also diminish the taste of the nutritionalcomposition. These phenomena often follow non-linear kinetics and theproblems quickly increase in magnitude when the concentration ofingredients is increased above 28 weight %. Therefore, many of thecommercial shelf-stable liquid products that are currently availablehave intact protein levels below about 9 g per 100 ml of product.

A known solution to the problem how to increase the protein levels to ahigher level without imparting viscosity is replacing part of the totalprotein by peptides or free amino acids. However, this seriouslydecreases taste appreciation and therefore voluntary intake of thenutritional composition by the patient group.

On the other hand, many concentrates like condensed milks suffer from anincomplete nutrient profile, too high lactose levels, sticky mouth-feel,high viscosity, extreme sweetness and a high osmotic value, which is notappreciated by the consumer and increases rapidly feelings of fullnessand satiety after consumption. This makes that the urge to consume morevolume deteriorates rapidly once a small amount of the product has beenconsumed.

EP 0 486 425 A2 (Sandoz Nutrition, published 20 May 1992) discloses aliquid nutritional composition comprising 3.9 weight % of WPC having anenergy density of 1.0 kcal/ml.

EP 0 747 395 (Nestle S. A, published 11 Dec. 1996) discloses a productfor treating renal patients having an energy density of 1.6-2.25 kcal/mland comprising free amino acids and whey proteins, wherein the ratio ofessential amino acids to non-essential amino acids is 2-4:1. By usingfree amino acids, the amino acid composition is improved withoutincreasing the viscosity. However, the taste is not acceptable forcachectic persons or other persons which have difficulties in eating theproper volume of food. The amount of protein is about 3 to 4 g/100 ml ofproduct.

EP 1 314 361 (Nestec S. A., published 28 May 2005, also published as US2003/099761) discloses a nutritionally complete calorically denseformula comprising maximum 8 g/100 ml intact whey protein using WPI as asource of whey (Example 1). An intermediate composition containing 9.2weight. % whey protein is acidified to a pH of 3.0, UHT treated at 148°C. for 5 seconds followed by dilution with a base to pH 6.8. Thissolution is subsequently mixed with the usual ingredients (lipids,carbohydrates, minerals) to provide a nutritional composition.

WO 2007/110411 and WO 2007/110421 (Nestec S. A., published Oct. 4, 2007)disclose heat-treated whey protein micelles, obtained by a process whichcomprises a pH adjustment and a heat-treatment between 70° C. and 95° C.

EP 1 787 528 (Kraft Foods Holdings Inc, published May 23, 2007)discloses a method of deflavoring whey protein using membraneelectrodialysis. The deflavored whey protein materials are said to besuitable for use in dairy and non-dairy beverages, smoothies, healthdrinks, cheese cheese analogs, dairy and non-dairy yoghurts, meat andmeat analog products, cereals, baked products, snacks and the like. Thedocument mentions the use of the deflavored whey protein in liquid foodproducts to provide about 2.5 to about 30 g whey protein per singleliquid serving of about 100 to about 300 ml. However, the document doesnot disclose how to prepare liquid food products with a highconcentration of protein that enables achieving stable liquid foodproducts upon sterilization or pasteurization. Without takingappropriate measures, it is not possible to prepare sterilized orpasteurized liquid food products with a whey protein concentration offor example 30 g per 100 ml.

SUMMARY OF THE INVENTION

In one embodiment, the present invention relates in general to ashelf-stable liquid enteral composition for providing nutrition, eitheras a supplement, or as a complete nutrition, with a high protein contentof a non-hydrolysed globular protein, in particular a whey protein.

In one embodiment, the present invention provides a shelf-stable liquidenteral nutritional composition based mainly on non-hydrolysed globularproteins, designed to meet the nutritional needs of persons in needthereof, in particular elderly, persons recovering from certain diseasestates, and malnourished persons. The composition provides an increasedamount of proteins per unit volume while providing a sufficiently lowviscosity to allow the composition to be easily consumed orally or beadministered by tube. In addition, the taste of the composition is notdiminished in comparison with a less concentrated composition based onnon-hydrolysed whey proteins.

To this end, in a first embodiment of the present invention, a liquidenteral nutritional composition is provided, in particular a sterilizedor pasteurized liquid enteral nutritional composition, comprising i) 9to 20 g of non-hydrolysed globular protein per 100 ml of the compositionhaving a pH>3 and ≦8; ii) 10 to 20 g of non-hydrolysed globular proteinper 100 ml of the composition; iii) 9 to 20 g of non-hydrolysed globularprotein per 100 ml of the composition, with the proviso that aUHT-sterilized composition comprising 9.2 weight % whey protein having apH=3 is excluded. In particular, said globular protein is a wheyprotein.

In a second embodiment, the present invention concerns a method ofproviding nutrition to a person in need thereof, in particular elderly,persons recovering from certain disease states, and malnourishedpersons, comprising the steps of administering to said person thenutritional composition according to the present invention.

In a third embodiment, the present invention concerns a process for theheat-treatment of non-hydrolysed globular proteins, to obtainheat-treated non-hydrolysed globular proteins with unique properties. Inparticular, said heat-treated non-hydrolysed globular protein is a wheyprotein.

The unique properties allow not only the manufacture of a nutritionalcomposition comprising 9 to 20 g of heat-treated non-hydrolysed globularper 100 ml of the composition, but the unique heat-treatednon-hydrolysed globular protein is suitable for use in any nutritionalcomposition comprising these unique heat-treated globular proteins as aprotein source in any concentration. Therefore, in a fourth embodiment,the present invention concerns the unique heat-treated non-hydrolysedglobular proteins per se, obtainable by the process according to theinvention, and any product, formulation or composition comprising saidheat-treated globular proteins, in particular whey proteins.

The invention will now be further elucidated by describing a number ofembodiments of the present invention.

DETAILED DESCRIPTION OF THE INVENTION Globular Proteins

The invention is generally concerned with globular proteins. Globularproteins may be single chains, two chains or more chains which interactin the usual ways or there may be portions of the chains with helicalstructures, pleated structures, or completely random structures.Globular proteins are relatively spherical in shape as the name implies.They are distributed in both plant and animal tissues. For instance,albumins can be found in blood (serum albumin), milk (lactalbumin), eggwhite (ovalbumin), lentils (legumelin), kidney beans (phaseolin), andwheat (leucosin). Globulins can be found in blood (serum globulins),muscle (myosin), potato (tuberin), Brazil nuts (excelsin), hemp(edestin), whey (lactoglobulins, immunoglobulins, and lactoferrins), peaand lentils (legumin, vicilin), and soy. Also, many enzymes and othervegetable proteins are globular proteins.

More specifically, the invention is concerned with pea, soy and wheyproteins, more in particular with whey proteins.

Whey Proteins

One of the most superior classes of food protein is whey protein. It isknown for its excellent amino acid profile, high cystein content, rapiddigestion, and interesting bioactive proteins (lactoglobulins,immunoglobulins, and lactoferrins). Nutritionally speaking, whey proteinis known as a naturally complete protein because it contains all of theessential amino acids required in the daily diet. It is also one of therichest sources of branched chain amino acids (BCAAs, in particularleucine) which play an important role in muscle protein synthesis.Moreover, some of the individual components of whey protein have beenshown to prevent viral and bacterial infection and modulate immunity inanimals. Whey protein is the preferred choice of proteins to treatpersons suffering from sarcopenia, but is also suitable for healthypersons, such as sportsmen and active elderly.

As a source of whey protein to be used in the present invention, anycommercially available whey protein source may be used, i.e. wheyobtained by any process for the preparation of whey known in the art, aswell as whey protein fractions prepared thereof, or the proteins thatconstitute the bulk of the whey proteins being β-lactoglobulin,α-lactalbumin and serum albumin, such as liquid whey, or whey in powderform, such as whey protein isolate (WPI) or whey protein concentrate(WPC). Whey protein concentrate is rich in whey proteins, but alsocontains other components such as fat, lactose and glycomacroprotein(GMP), a caseine-related non-globular protein. Typically, whey proteinconcentrate is produced by membrane filtration. On the other hand, wheyprotein isolate consists primarily of whey proteins with minimal amountsof fat and lactose. Whey protein isolate usually requires a morerigorous separation process such as a combination of microfiltration andultra-filtration or ion exchange chromatography. It is generallyunderstood that a whey protein isolate refers to a mixture in which atleast 90 weight % of the solids are whey proteins. A whey proteinconcentrate is understood as having a percentage of whey proteinsbetween the initial amount in the by-product (about 12 weight %) and awhey protein isolate. In particular, sweet whey, obtained as aby-product in the manufacturing of cheese, acid whey, obtained as aby-product in the manufacturing of acid casein, native whey, obtained bymilk microfiltration or rennet whey, obtained as a by-product in themanufacturing of rennet casein, may be used alone or in combination assource of globular whey proteins.

Furthermore, whey proteins may originate from all kinds of mammaliananimal species, such as, for instance cows, sheep, goats, horses,buffalo's, and camels. Preferably, the whey protein is of bovine origin.

Preferably, the whey protein source is available as a powder, preferablythe whey protein source is a WPC or WPI.

Whey protein isolate consists mainly of a mixture of β-lactoglobulin(about 65 weight %), α-lactalbumin (about 25 weight %) and serum albumin(about 8 weight %). These proteins are globular proteins that aresensitive to aggregation in the denaturated state. The denaturationtemperature of β-lactoglobulin is pH-dependent; at pH 6.7, irreversibledenaturation occurs when the protein is heated at temperatures above 65°C. In the denaturated state, a free thiol group is exposed. This freethiol group can initiate inter-protein disulfide interactions leading toa polymerization reaction resulting in aggregate formation. Also twodisulfide bridges, present in native β-lactoglobuline, are involved inthe polymerization reaction and also other sulphur containing groupsincluding cysteine residues are thought to play a role.

α-Lactalbumin also has a denaturation temperature of about 65° C. Sinceα-lactalbumin does not have a free thiol group (only four disulfidebridges), solutions of pure α-lactalbumin are not irreversiblydenaturated under most processing conditions. However, in the presenceof β-lactoglobulin, as is the case in e.g. a whey protein concentrate orisolate, α-lactalbumin is more sensitive to irreversible denaturationthrough the formation of α-lactalbumin/β-lactoglobulin complexes inwhich also disulfide bridges in β-lactoglobuline and α-lactalbumin areinvolved via interchange reactions. Also the circumstance thatα-lactalbumin contains cystein residues is considered to contribute to acertain sensitivity to irreversible denaturation.

Denaturated β-lactoglobulin and α-lactalbumin are both sensitive tocalcium; this is particularly the case in the pH range of about 5 toabout 8 where the protein carries a neutral to net negative charge. AtpH 4, the protein carries a net positive charge and is less sensitive tocalcium-induced aggregation.

The size, shape and density of the protein aggregates are influenced bya number of environmental and processing parameters includingtemperature, heating rate, pressure, shear, pH and ionic strength.Depending on the combination of these parameters, the aggregates mayform a space-filling network (gel), fibrils or compact micro-particles.For example microparticulated whey can be formed under specific ionicstrength and shear conditions. These particles have a compact structure,a high intrinsic viscosity and a low specific volume. Further, it isknown that a relationship exists between aggregates size and heatingtemperature for microparticulated whey produced under shear conditions.Microparticulated whey protein has received a lot of interest lately forapplication as a fat replacer or viscosity enhancer for yoghurt.

One of the major problems encountered with the production of liquidready-to-use compositions containing globular proteins in general, andwhey proteins in particular, is their limited processability andheat-sensitivity. As these proteins are heated above their denaturationtemperature in a sterilization process, they unfold and are transformedinto a reactive state, polymerize into aggregates or gels. As aconsequence, the heat-treated liquid composition exhibits unwantedsensorial attributes like chalkiness, sandiness, lumpiness. Besides, theshelf life of these products is limited in that sediment and/or creamlayers are formed soon after production. In a composition with a highglobular protein content, in particular whey, these instabilities areeven more pronounced and result in products with an unwanted highviscosity and extensive fouling and blocking of the UHT heatingequipment.

Surprisingly, the inventors have now found that it is possible toprepare a pasteurized or sterilized liquid enteral nutritionalcomposition having a long shelf life by means of a method wherein acomposition that comprises mainly globular proteins as a protein source,in particular whey proteins, is subjected to a specific heat-treatmentthat comprises the steps of converting the composition into an aerosoland quickly heating and cooling said aerosol to obtain a composition ofunique heat-treated globular proteins, in particular whey proteins. Thusthe present invention concerns a pasteurized or sterilized liquidenteral nutritional composition. Also the present invention concerns amethod for the preparation of a pasteurized or sterilized liquid enteralnutritional composition, which comprises the method for theheat-treatment of non-hydrolysed globular proteins, in particular wheyproteins, as described below.

Without being bound (or restricted) to any theory, it is believed thatraising the temperature quickly to a temperature well above thedenaturation temperature of the whey protein, leads to denaturation ofwhey protein. The thiol group of β-lactoglobulin, the main constituentof whey protein, is being exposed and termination reactions formingdisulfide bridges dominate initially after heating. As a result, small,compact whey protein particles are formed which are largely inert in anyfurther heat-treatment. On the contrary, in a heat-treatment just abovethe denaturation temperature of the whey, the aggregation reaction islimited by the rate of unfolding of the protein, leading to extensivepolymerization and voluminous protein aggregates. Also, when the whey isheated to high temperatures (i.e. far above the protein denaturationtemperature, for example at 110° C.) via a slow heating process, i.e. aprocess in which the temperature of the protein solution is raisedgradually, for example 0.1 to 2° C. per second, using e.g. retort, plateor tubular heat exchangers, the whey exhibits extensive polymerizationduring heating up when process temperatures pass the temperature windowjust above the denaturation temperature of the whey protein. As aresult, the product is too thick, lumpy, sandy and extensive fouling isobserved in the heating apparatus.

Thus surprisingly, it was found that the time for whey proteins to bespent in a temperature window just above the denaturation temperature,should be minimized.

Method of Heat Treatment

The non-hydrolysed globular proteins, in particular whey proteins, aresubjected to a heat-treatment, comprising the consecutive steps of:

-   -   a) adjusting the pH of an aqueous composition comprising        non-hydrolysed globular proteins to a value of between about 2        and 8;    -   b) converting the composition comprising non-hydrolysed globular        proteins obtained in step a) into an aerosol;    -   c) subjecting the aerosol obtained in step b) to a temperature        of 100 to 190° C. during a time of about 30 to 300 milliseconds;    -   d) flash-cooling the heat-treated aerosol obtained in step c) to        a temperature below 85° C. to obtain an aqueous solution        comprising heat-treated globular proteins.

It is emphasized that the aqueous composition comprising non-hydrolysedglobular proteins may contain, next to non-hydrolysed globular proteins,in particular whey, any other nutritional ingredients, such as otherproteins, amino acids, fat, carbohydrates, fibers, minerals, vitamins,and the like, and that these ingredients may be present when subjectingthe aqueous composition to the method according to the invention, inparticular step b).

In one embodiment, the pH of the aqueous composition of non-hydrolysedglobular proteins in step a) >3 and ≦8.

In one embodiment, the pH of the aqueous composition of non-hydrolysedglobular proteins in step a) is about 2 to 5. More preferably, the pH ofthe aqueous composition of non-hydrolysed globular proteins in step a)is about 4.

In yet another embodiment, the pH of the aqueous composition ofnon-hydrolysed globular proteins in step a) is about 6 to 8. Morepreferably, the pH of the aqueous composition of non-hydrolysed globularproteins in step a) is about 7.

Preferably, said globular proteins are whey proteins.

In one embodiment in step c) the aerosol is subjected to a temperatureof 100 to 190° C. during a time of at least 30, or about 40, about 50,about 60, about 70, about 80, about 90 or about 100 milliseconds to atmost about 280, about 260, about 240, about 220, about 200, about 190,about 180, about 170, about 160 or about 150 milliseconds.

In one embodiment in step c) the aerosol is subjected to a temperatureof at least about 110, about 120, about 130, about 140, about 150, about160, about 170 or about 180° C.

In one embodiment, the aerosol obtained in step b) is subjected to atemperature of 110 to 180° C., during a time of about 30 to 200milliseconds, more preferably 40 to 150 milliseconds, more preferably 80to 120 milliseconds. In another embodiment, the aerosol obtained in stepb) is subjected to a temperature of 110° C., during a time of about 30to 200 milliseconds, more preferably 40 to 150 milliseconds, morepreferably 80 to 120 milliseconds. In yet another embodiment, theaerosol obtained in step b) is subjected to a temperature of 170° C.,during a time of about 30 to 200 milliseconds, more preferably 40 to 150milliseconds, more preferably 80 to 120 milliseconds.

In one embodiment, in step a) the pH of an aqueous composition ofnon-hydrolysed whey proteins is adjusted to a value of about 4 (acidwhey solution), and the aerosol obtained in step b) is subjected to atemperature of 110° C., during a time of about 30 to 200 milliseconds,more preferably 40 to 150 milliseconds, more preferably 80 to 120milliseconds.

In another embodiment, in step a) the pH of an aqueous composition ofnon-hydrolysed whey proteins is adjusted to a value of about 7 (neutralwhey solution), and the aerosol obtained in step b) is subjected to atemperature of 170° C., during a time of about 20 to 200 milliseconds,more preferably 40 to 150 milliseconds, more preferably 80 to 120milliseconds.

In one embodiment, in step c), the conversion of the composition ofnon-hydrolysed globular proteins obtained in step a) into an aerosol isdone using a spray nozzle, as described below in detail.

In one embodiment, step d) is performed by transporting the aerosol intoa vacuum chamber (flash-cooling) to remove an amount of water byevaporation, equivalent to the amount of steam used and the product iscooled by indirect cooling to a temperature of less than about 85° C.,preferably less than about 60° C. This method allows fast cooling andquick removal of volatiles (i.e. steam). The cooling preferably takesplace nearly instantaneously, i.e. in a time window preferably ofmilliseconds. In one embodiment, the aqueous solution comprisingheat-treated globular proteins obtained in step d) is comprised in theliquid nutritional composition according to the invention. Thus in oneembodiment the aqueous solution comprising heat-treated globularproteins obtained in step d) comprises an amount of water equivalent tothe amount of water obtained in step a).

It is without saying that any of the aforementioned preferred values(pH, temperature and time) and ranges thereof for each of the steps a),b), c) and d) may be combined in an intelligent manner, withoutdeparting from the scope of the invention.

A similar, albeit fundamentally differently operated method has beendisclosed in EP 1 351 587 (Nutricia N. V, also published as US2004/0057867). This document discloses a method for sterilization orpasteurization of heat-sensitive proteins such as whey protein. Themethod uses a spray-cooking apparatus, wherein a liquid product issubjected to superheated steam. The time of heating is less than 20milliseconds. Such a period of time was found sufficient to killmicroorganisms to a desired degree. The method described in thisdocument is in particular designed to produce powders upon drying in aspray tower. This document does not disclose or suggest to collect aliquid aqueous nutritional composition. Although a similar apparatus wasused in the examples of the present application, the apparatus wasoperated differently, a first major difference being that a liquidaqueous composition is obtained and a second essential difference beingthat the aerosol is subjected to heat for a longer time. According tothe method of the present invention a longer duration of heating time isnecessary. Apparently, sufficient time is required to allow theformation of small, compact whey proteins to take place, making itpossible to produce sterilized or pasteurized liquid enteral nutritionalcompositions containing high concentrations of whey proteins.

Apparatus

The apparatus to carry out the invention may be selected by the skilledperson based on the steps described above. Basically, the apparatus tocarry out the invention comprises a nozzle for atomizing the composition(step b), a chamber to heat the aerosol (step c), and a chamber to coolthe heated aerosol (step d). Preferably, the heating is done by mixingthe aerosol with steam of a certain temperature (and at a certain steampressure). When using steam, the apparatus may comprise a nozzle and amixing chamber. A mixing chamber generally comprises one or more inflowopenings for steam flows and for product flows, in which a product flowmay optionally be premixed with a part of the steam. It may bepreferable to select the mixing chamber such that only one product flowis atomized with one steam flow, since this simplifies the cleaning ofthe mixing chamber after use.

A schematic representation of a suitable nozzle for atomizationaccording to the invention is shown in EP 1351587, FIG. 1, in which anozzle with mixing chamber is shown. Said FIG. 1 is included herein byreference. It turns out that a nozzle with mixing chamber can be veryeffectively used for the heat treatment of a product. A suitable mixingchamber is generally characterized in that steam and atomized product tobe treated are mixed, while the volume throughput of the steam will bemuch greater than that of the atomized product to be treated and theresidence time of the atomized product is sufficiently to obtain thedesired heat-treated globular protein. The volume ratio between thesteam flow and the product flow may range between, for instance, about20:1 and 150:1. It is important that the pressure in the mixing chamberis higher than in the space to which the atomized product is passed.

The form and size of the inflow openings for the steam flow (1) and theflow of the product in liquid form (2) in the mixing chamber and theirmutual position are selected such that intensive mixing takes placebetween product and steam. It is noted that the inflow openings can beplaced such that the steam flow and the product flow enter the mixingchamber in substantially parallel direction. This may take place in botha horizontally, vertically and diagonally manner. However, it is alsopossible that the steam flow and the product flow enter the mixingchamber at different angles, for instance a vertical steam flow and ahorizontal product flow. The inflow openings are further arranged suchthat the product is atomized in small droplets, which after a shortresidence time in the mixing chamber (4) leave the mixing chamberthrough an outflow opening (5), for instance to a cooling chamber (6).The inflow opening(s) for the steam flow preferably contain a steamdistribution plate (3). By changing the dimensions of the mixing chamberand/or the outflow opening(s) in the manner known to those skilled inthe art, the average residence time and particle size of the atomizeddroplets can be varied. To set a suitable residence time in the mixingchamber is a simple matter of optimization for the skilled person anddepends at least on the temperature and pressure in the mixing chamber.

The mixing is preferably realized by contacting the atomized productflow and the steam flow close to the inflow opening of the product inthe mixing chamber and bringing the steam at high speed around theatomized product. In a preferred embodiment, such a mixing takes placeby bringing the steam near the product concentrically around the inflowopening of atomized product in the mixing chamber. The product flow tosteam flow ratio can be varied in a ratio of 1.6 to 10 kg product inliquid form per kg steam. Very good results are realized at a wetproduct flow to steam flow ratio of 2.4 to 8 kg product in liquid formper kg steam.

In principle, any type of mixing chamber is suitable in which steam andproduct can be mixed and atomized. Very suitable for mixing andatomizing a product-steam mixture according to the invention is a nozzlesuch as “two-fluid” type nozzle, an example of which is described in EP0438783, FIG. 1. This nozzle contains a small chamber at the end of aproduct line in which steam and product are combined. To increase thecapacity, more nozzles can be used in a parallel arrangement.

The temperature of the supplied saturated or superheated steam in themethod according to the invention is preferably in the range of 100 and190° C., more preferably between 100 and 180° C., still more preferablybetween 100 and 170° C. In general, the temperature in the mixingchamber will be maintained at the desired level through the steam,although it is also possible that the mixing chamber itself is heated byanother heat source.

Good results are obtained when introducing the steam into the mixingchamber at a steam pressure of 1.5 to 10 bar, and in particular at asteam pressure of 1.8 to 8.2 bar, in mixing chambers about 1 to 20 cm inlength. This pressure is preferably measured just before the steam isintroduced into the mixing chamber via a spray nozzle.

Preferably, the particle size (aggregate size) of the flash-cooledaerosol (obtained in step d) is less than about 30 μm, more preferablyless than about 10 μm, still more preferably less than 5 μm, and mostpreferably less than 1 μm. At particle diameters above 30 μm, thenutritional composition may start to taste sandy, which is not favoured.

Depending on the temperature/time combination, the method according tothe invention may not provide sufficient pasteurization orsterilization. For instance, 100 milliseconds at 110° C. does notprovide sufficient microbial sterility for a neutral product. However,100 milliseconds at 170° C. would provide sufficient sterility.

In one embodiment, the product obtained from step d) is furtherpasteurized using conventional equipment such as a plate or tubular heatexchanger, scraped surface heat exchanger or a retort to give the finalproduct. Most excellent results are obtained when using a plate heatexchanger. The invention therefore also relates to the above describedmethod according to the invention, comprising steps a), b), c) and d),subsequently comprising a pasteurization step using a plate heatexchanger. The plate heat exchanger is preferably operated at 92° C. for30 seconds.

In another embodiment, a sterile product is obtained from step d) orfrom the above mentioned subsequent pasteurization step, which can befilled aseptically in aseptic containers in a further process step.

Nutritional Composition

Surprisingly, this invention makes it possible to produce a liquidenteral nutritional composition with a high content of non-hydrolysedglobular protein, in particular whey protein, with a long shelf life andwith a low viscosity.

In the context of this application, “non-hydrolysed” proteins isequivalent to “intact” proteins, meaning that the proteins have not beensubjected to an hydrolysis process. However, minor amounts of hydrolysedproteins may be present in the source of non-hydrolysed proteins, or maybe added to the formulation, such as additional amino acids, such as,for example leucine, isoleucine, and the like. In this context, “minor”should be understood as an amount of about 20 weight % or less, forexample of about 10 weight % or less. The term “about” should beinterpreted as a deviation of plus or minus 10% of the given value.

Hence, in an embodiment of the invention, a liquid enteral nutritionalcomposition comprising 10 to 20 g of non-hydrolysed globular proteinsper 100 ml of the composition is provided.

Also, in an embodiment of the invention, a liquid enteral nutritionalcomposition having a pH >3 and ≦8 comprising 9 to 20 g of non-hydrolysedglobular proteins per 100 ml of the composition is provided.

Also, in an embodiment of the invention, a liquid enteral nutritionalcomposition comprising 9 to 20 g of non-hydrolysed globular protein per100 ml of the composition is provided, with the proviso that aUHT-sterilized composition comprising 9.2 weight % whey protein having apH=3 is excluded.

Preferably, the globular proteins are whey proteins. In anotherembodiment, the amount of non-hydrolysed globular proteins is 9, 10, 11,12, 13, 14, 15, 16, 17, 18, 19 or 20 gram per 100 ml of the composition,or any value in between the aforementioned values.

In one embodiment, the pH of the liquid enteral nutritional compositionis about 2 to about 8. In one embodiment, the pH of the liquid enteralnutritional composition is >3 and ≦8. In another embodiment, the pH isabout 2, 3, 4, 5, 6, 7, or 8 or any value in between the aforementionedvalues.

In a specific embodiment of the composition according to the invention,the composition is acidic (yoghurt-like or juice-like) with a pH ofabout 4. Acidification may be achieved by any method known to theskilled person, such as the addition of an acid (such as, for instancelactic acid, citric acid, phosphoric acid) or through fermentation. Thethus obtained composition has a pleasant mild acidic taste which can beflavoured perfectly with a fruity flavour.

In a further specific embodiment of the invention, the composition has aneutral pH (i.e. a pH of about 7). The thus obtained composition has apleasant taste which may optionally be flavoured with e.g. vanilla,chocolate, caramel, banana, strawberry.

According to another embodiment of the present invention, the proteinprovides 10% to 50%, preferably at least 15%, more preferably at least20%, at least 25%, at least 30% of the total energy content of thecomposition. The % of total energy is also abbreviated as En %; En % isthus short for energy percentage and represents the relative amount thata constituent contributes to the total caloric value of the composition.The high levels of protein are beneficial for patients who may not bephysically capable of receiving a large volume, for example, fluidrestricted patients. Such patients can be given a reduced level of fluidwhile still receiving a required amount of nutritional support per day.

In the context of this application, the term “at least” also includesthe starting point of the open range. For example, an amount of “atleast 95 weight %” means any amount equal to 95 weight % or above.

In one embodiment of the present invention, the composition has anenergy density of at least 0.36 kcal/ml, preferably at least 1.0kcal/ml, preferably at least 1.5 kcal/ml, preferably at least 2.0kcal/ml, more preferably at least 2.4 kcal/ml. Although the compositionhas a high energy density, it also has a sufficiently low viscosity toallow it to be consumed by persons that may have difficulty swallowingproducts or those that are tube fed.

In one embodiment of the present invention, the amount of whey proteinsin the liquid nutritional composition according to the invention is atleast 85 weight %, more preferably at least 90 weight %, more preferablyat least 95 weight % of the total protein present in the liquidnutritional composition.

In a further embodiment of the present invention, the composition maycomprise up to about 40 weight % of a non-globular protein, such ascasein, caseinate, micellar casein isolate and the like, and any mixturethereof, preferably less than or equal to 20 weight %, more preferablyless than or equal to 10 weight % of the total protein present in theliquid nutritional composition.

In one embodiment of the present invention, the composition may comprisea free amino acid, or a mixture of free amino acids, up to 5 g/100 ml,more preferably less than 2 g/100 ml, more preferably less than 1 g/100ml, most preferably less than 0.5 g/100 ml

The composition according to the invention is designed to eithersupplement a person's diet or to provide complete nutritional support.Hence, the composition according to the invention may further compriseat least fat and/or carbohydrate and/or a source of vitamins andminerals and/or a source of prebiotics. Preferably, the compositionaccording the invention is a nutritionally complete composition.

Fat

In one embodiment of the present invention, the liquid nutritionalcomposition according to the invention further comprises fat, said fatproviding between 20 to 40% of the total energy content of thecomposition. For a 1.6 kcal/ml composition, this amounts to 32 to 64kcal per 100 ml. For a 2.4 kcal/ml composition, this amounts to 48 to 96kcal per 100 ml.

The fat may include medium chain triglycerides (MCT, mainly 8 to 10carbon atoms long), long chain triglycerides (LCT) or any combination ofthe two types. MCTs are beneficial because they are easily absorbed andmetabolized in a metabolically-stressed patient. Moreover, the use ofMCTs will reduce the risk of nutrient malabsorption. LCT sources, suchas canola oil, rapeseed oil, or corn oil are preferred because they canreduce immune suppression associated with certain types of fatty acidsconcentrated in the body.

Preferably, the fat comprises 30 to 60 weight % of animal or algal fat,40 to 70 weight % of vegetable fat and optionally 0 to 20 weight % ofMCTs based on total fat of the composition. The animal fat preferablycomprises a low amount of milk fat, i.e. lower than 6 weight %,especially lower than 3 weight %. In particular, a mixture of corn oil,egg oil, and/or canola oil and specific amounts of marine oil are used.Egg oils, fish oils and algal oils are a preferred source ofnon-vegetable fats. Especially for compositions that are to be consumedorally, in order to prevent formation of off-flavours and to decrease afishy after-taste, it is recommended to select ingredients that arerelatively low in docosahexanoic acid (DHA), i.e. less than 6 weight %,preferably less than 4 weight % of the fat. Marine oils containing DHAare preferably present in the composition according to the invention inan amount lower than 25 weight %, preferably lower than 15 weight % ofthe fat. On the other hand, inclusion of eicosapentanoic acid (EPA) ishighly desirable for obtaining the maximum health effect. The amount ofEPA ranges preferably between 4 weight % and 15 weight %, morepreferably between 8 weight % and 13 weight % of the fat. The weightratio EPA:DHA is advantageously at least 6:4, for example between 2:1and 10:1.

Also, the liquid nutritional composition according to the invention maybeneficially comprise an emulsifier. Commonly known emulsifiers may beused, such as lecithin, and generally the emulsifier contributes to theenergy content of the fat in said composition.

Carbohydrates

In one embodiment of the present invention, the liquid nutritionalcomposition according to the invention further comprises carbohydrate,said carbohydrate providing between 30 to 60% of the total energycontent of the composition. Preferably, the carbohydrate provides atleast 40% of the total energy content of the composition according tothe invention.

The composition of the carbohydrate preferably is such that highviscosities, excessive sweetness, excessive browning (Maillardreactions) and excessive osmolarities are avoided. Acceptableviscosities and osmolarities may be achieved by adjusting the averagechain length (average degree of polymerisation, DP) of the carbohydratesbetween 1.5 and 6, preferably between 1.8 and 4. In order to avoidexcessive sweetness, the total level of sucrose and fructose is lessthan 52% and preferably less than 40% of the weight of the carbohydrate,especially of the digestible carbohydrate. Long-chain digestiblecarbohydrates such as starch, starch fractions and mild starchhydrolysates (DP≧6, DE<20), may also be present, preferably in an amountof less than 25 weight %, especially less than 15 weight % of thecarbohydrate, and less than 6 g/100 ml, preferably less than 4 g/100 mlof the total liquid enteral composition according to the invention.

In one embodiment of the present invention, the carbohydrate includesmaltodextrose with a high DE (dextrose equivalent). In one embodimentthe carbohydrate includes maltodextrose with a DE of >20, preferably >30or even >40, such as a DE of about 47. In one embodiment of the presentinvention, the carbohydrate includes maltodextrose with a high DE in anamount of at least 35 weight %, preferably at least 50 weight %,preferably at least 65 weight %, preferably at least 90 weight % of thetotal weight of carbohydrate. In one embodiment of the presentinvention, the carbohydrate includes maltodextrose with a low DE of 2 to20. In one embodiment of the present invention, the carbohydrateincludes maltodextrose with a low DE of 2 to 10, preferably with a lowDE of about 2. In one embodiment of the present invention, thecarbohydrate includes maltodextrose with a low DE in an amount of lessthan 35 weight %, preferably less than 20 weight %, preferably less than10 weight % of the carbohydrate. Maltodextrose with a low DE may also bereferred to as maltodextrine. In another embodiment of the presentinvention, the carbohydrate includes maltodextrose with a high DE,preferably a DE of >20, preferably >30 or even >40, most preferably a DEof about 47 in combination with maltodextrose with a low DE, preferablya low DE of 2 to 20, more preferably a low DE of 2 to 10, mostpreferably with a low DE of about 2. As is known, maltodextrose with alow DE, such as of about 2, gives rise to a high viscosity.Maltodextrose with a high DE, such as of about 47 gives rise to a lowviscosity, but is very sweet. The combination of both maltodextrosesoptimizes the balance between sweetness and viscosity. In one embodimentof the present invention, the carbohydrate includes at least 65 weight%, preferably at least 90 weight %, based on total weight ofcarbohydrate of maltodextrose with a DE>40, preferably with a DE ofabout 47 and 0 to 10 weight % of maltodextrose with a DE 2 to 10,preferably with a DE of about 2.

In another embodiment of the present invention, the carbohydrateincludes trehalose. As was indicated, it is one of the main objects ofthe invention to provide a nutritional composition with a low viscosity.Sucrose is very well suited for such purpose, but gives rise to verysweet compositions, which are in general disliked by the consumer.Maltodextrose with a low DE, such as of about 2, does not suffer fromthe latter drawback, but gives rise to a high viscosity. Maltodextrosewith a high DE, such as of about 47 gives rise to a low viscosity, butis again very sweet, and gives further rise to the undesired Maillardreactions. Trehalose is a preferred choice of carbohydrate, as it givesrise to a low viscosity, no undesired Maillard reactions and it has asweetness about half of that of sucrose. In one embodiment of thepresent invention, the carbohydrate includes trehalose in an amount of20% to 60% of the weight of the carbohydrate, in an amount of 20% to45%, more preferably in an amount of 25% to 45% of the weight of thecarbohydrate.

Vitamins and Minerals

The composition according to the invention may contain a variety ofvitamins and minerals. Overall, the composition according to theinvention preferably includes at least 100% of the United StatesRecommended Daily Allowance (USRDA) of vitamins and minerals in a onelitre portion.

In one embodiment of the present invention, the composition according tothe invention provides all necessary vitamins and minerals. For example,the composition according to the invention preferably provides 6 mg ofzinc per 100 ml of the composition which is beneficial for tissue repairin a healing patient. Preferably, the composition according to theinvention (also) provides 25 mg of vitamin C per 100 ml of thecomposition to aid patients with more severe healing requirements.Further, preferably, the composition according to the invention (also)provides 2.25 mg iron per 100 ml of the composition. Iron is beneficialin maintaining bodily fluids as well as circulatory system functions inan elderly patient.

In another embodiment of the present invention, the amount of divalentions ranges between 170 mg/100 ml and 300 mg/100 ml and preferablybetween 180 mg/100 ml and 280 mg/100 ml. Preferably, the amount ofcalcium ranges between 155 mg/100 ml and 300 mg/100 ml and preferablybetween 190 mg/100 ml and 250 mg/100 ml. The phosphorus content can beabove 10 mg per g of protein, with a calcium to phosphorus weight ratiobetween 1.0 and 2.0, preferably between 1.1 and 1.7. Carnitin mayadvantageously be present in an amount of 8 mg/100 ml to 1000 mg/100 ml,preferably 10 mg/100 ml to 100 mg/100 ml of composition; it may have theform of carnitin, alkyl carnitin, acyl carnation or mixtures thereof.Organic acids are preferably present at a level of between 0.1 g/100 mlto 6 g/100 ml, especially 0.25 g/100 ml to 3 g/100 ml. These acidsinclude short fatty acids such as acetic acid, hydroxy acids such aslactic acid, gluconic acid, and preferably polyvalent hydroxy acids,such as malic acid and citric acid. In one embodiment of the presentinvention, the present composition also comprises citric acid.

Prebiotics

The liquid enteral nutritional composition according to the inventionmay be fortified with a prebiotic, for example, with non-digestiblecarbohydrates (dietary fibres), such as fructo-oligosaccharides and/orinulin. In an embodiment, the composition according to the inventioncomprises 0.5 g/100 ml to 6 g/100 ml of non-digestible carbohydrates.Herein non-digestible carbohydrates are also referred to as dietaryfibres. The dietary fibres include non-digestible oligosaccharideshaving a DP of 2 to 20, preferably 2 to 10. More preferably, theseoligosaccharides do not contain substantial amounts (less than 5 weight%) of saccharides outside these DP ranges, and they are soluble. Theseoligosaccharides may comprise fructo-oligosaccharides (FOS),trans-galacto-oligosaccharides (TOS), xylo-oligosaccharides (XOS), soyoligosaccharides, and the like. Optionally, also higher molecular weightcompounds such as inulin, cellulose, resistant starch and the like maybe incorporated in the composition according to the invention. Theamount of insoluble dietary fibre such as cellulose is preferably lowerthan 20 weight % of the dietary fibre fraction of the compositionaccording to the invention, and/or below 0.4 g/100 ml. The amount ofthickening polysaccharides such as carrageenans, xanthans, pectins,galactomannans and other high molecular weight (DP>50) indigestiblepolysaccharides is preferably low, i.e. less than 20% of the weight ofthe dietary fibre fraction, or less than 1 g/100 ml. Instead, hydrolysedpolysaccharides such as hydrolysed pectins and galactomannans canadvantageously be included.

A preferred dietary fibre component is an indigestible oligosaccharidewith a chain length (DP) of 2 to 10, for example Fibersol® (resistantoligoglucose), in particular hydrogenated Fibersol®, or a mixture ofoligosaccharides having a DP of 2 to 10, such as fructo-oligosaccharidesor galacto-oligosaccharides, which may also contain a small amount ofhigher saccharides (e.g. with a DP of 11 to 20). Such oligosaccharidespreferably comprise 50 weight % to 90 weight % of the fibre fraction, or0.5 g/100 ml to 3 g/100 ml of the composition according to theinvention. Other suitable fibre components include saccharides that haveonly partial digestibility.

Viscosity

In one embodiment of the present invention, the viscosity of the liquidenteral nutritional composition is lower than 500 mPa·s, measured at 20°C. (i.e. room temperature) at a shear rate of 100 s⁻¹, preferablybetween 10 and 200 mPa·s, more preferably between 10 and 100 mPa·s, mostpreferably below 50 mPa·s. The viscosity may suitably be determinedusing a rotational viscosity meter using a cone/plate geometry. Thisviscosity is ideal for orally administering the liquid enteralnutritional composition according to the invention because a person mayeasily consume a serving having a low viscosity such as that displayedby the present invention. This viscosity is also ideal for unit dosagesthat are tube fed.

In one embodiment of the present invention, the density of thecomposition ranges between 1.00 g/ml and 1.20 g/ml, especially between1.10 g/ml and 1.18 g/ml.

Dosage Unit

The liquid enteral nutritional composition according to the inventionmay have the form of a complete food, i.e. it can meet all nutritionalneeds of the user. As such, it preferably contains 1200 to 2500 kcal perdaily dosage. The daily dosage amounts are given with respect to a dailyenergy supply of 2000 kcal to a healthy adult having a body weight of 70kg. For persons of different condition and different body weight, thelevels should be adapted accordingly. It is understood that the averagedaily energy intake preferably is about 2000 kcal. The complete food canbe in the form of multiple dosage units, e.g. from 4 (250 ml/unit) to 20units (50 ml/unit) per day for an energy supply of 2000 kcal/day using aliquid enteral nutritional composition according to the invention of 2.0kcal/ml.

The liquid enteral nutritional composition can also be a foodsupplement, for example to be used in addition to a non-medical food.Preferably as a supplement, the liquid enteral nutritional compositioncontains per daily dosage less than 1500 kcal, in particular as asupplement, the liquid enteral nutritional composition contains 400 to1000 kcal per daily dose. The food supplement can be in the form ofmultiple dosage units, e.g. from 2 (250 ml/unit) to 10 units (50ml/unit) per day for an energy supply of 1000 kcal/day using a liquidenteral nutritional composition according to the invention.

In one embodiment of the present invention, a unit dosage comprises anyamount of the liquid enteral nutritional composition according to theinvention between 10 ml and 250 ml, the end values of this rangeincluded, preferably any amount between 25 ml and 200 ml, the end valuesof this range included, more preferably any amount between 50 ml and 150ml, the end values of this range included, most preferably about 125 ml.For example, a person receiving 50 ml unit dosages can be given 10 unitdosages per day to provide nutritional support using a liquid enteralnutritional composition according to the invention of 2.0 kcal/ml.Alternatively a person receiving 125 ml unit dosages can be given 4 or 5or 6 or 7 or 8 unit dosages per day to provide nutritional support usinga liquid enteral nutritional composition according to the invention.Such small dosage units are preferred because of better compliance.

In one embodiment of the present invention, the composition is providedin a ready to use liquid form and does not require reconstitution ormixing prior to use. The composition according to the invention can betube fed or administered orally. For example, the composition accordingto the invention can be provided in a can, on spike, and hang bag.However, a composition may be provided to a person in need thereof inpowder form, suitable for reconstitution using an aqueous solution orwater such that the composition according to the invention is produced.Thus in one embodiment of the present invention, the present compositionis in the form of a powder, accompanied with instructions to dissolve orreconstitute in an aqueous composition or water to arrive at the liquidnutritional enteral composition according to the present invention. Inone embodiment of the present invention, the present liquid nutritionalenteral composition may thus be obtained by dissolving or reconstitutinga powder, preferably in an aqueous composition, in particular water.

In one embodiment of the present invention, the composition according tothe invention is packaged. The packaging may have any suitable form, forexample a block-shaped carton, e.g. to be emptied with a straw; a cartonor plastic beaker with removable cover; a small-sized bottle for examplefor the 80 ml to 200 ml range, and small cups for example for the 10 mlto 30 ml range. Another suitable packaging mode is inclusion of smallvolumes of liquid (e.g. 10 ml to 20 ml) in edible solid or semi-solidhulls or capsules, for example gelatine-like coverings and the like.Another suitable packaging mode is a powder in a container, e.g. asachet, preferably with instructions to dissolve or reconstitute in anaqueous composition or water.

Preparation

The liquid enteral nutritional composition according to the inventionmay be prepared by the method as outlined in FIG. 1. Basically, the wheyprotein, carbohydrates and minerals are dispersed into water and the pHis adjusted using a suitable acid, such as lactic acid, citric acid,phosphoric acid and the like. The fat is blended into the product andthis pre-emulsion is homogenized. This aqueous emulsion is subsequentlyatomized using the method of the invention, flash-cooled and collected.Optionally, the final pH and dry matter of the emulsion may be adjusted.The resulting product is subsequently pasteurized or sterilized usingthe known methods, such as, UHT processes and filled into containers orpasteurized or sterilized in containers in a retort. The liquid enteralnutritional composition according to the invention may alternatively beprepared by the method as outlined in FIG. 7. Basically, the wheyprotein, carbohydrates and minerals are dispersed into water and the pHis adjusted using a suitable acid or base. The fat is blended into theproduct and this pre-emulsion is homogenized. This aqueous emulsion issubsequently atomized, flash-cooled and collected in an aseptic tankfrom which it can be filled into aseptic containers.

Effectivity

The present invention is also directed at the nutritional compositionaccording to the present invention for providing nutrition to a personin need thereof. The present invention also concerns a method ofproviding nutrition to a person in need thereof, comprising the steps ofadministering to said person the nutritional composition according tothe present invention. Said person may be an elderly person, a personthat is in a disease state, a person that is recovering from a diseasestate, or a person that is malnourished. Said person may also be ahealthy person, such as a sportsman or active elderly. In other words,the present invention concerns the use of the nutritional compositionaccording to the present invention in the manufacture of a compositionfor providing nutrition to a person in need thereof, preferably to anelderly person, a person that is in a disease state, a person that isrecovering from a disease state, a person that is malnourished or ahealthy person, such as a sportsman or active elderly.

In a further aspect, the present invention relates to the non-hydrolysedheat-treated globular protein per se obtainable by the process accordingto the invention, and any product, formulation or composition comprisingsaid heat-treated globular proteins, in particular whey proteins, in anyform, such as a solution, suspension, dispersion, nutritionalcomposition, medicament, or powder, in any concentration conceivable.

The invention will now be further elucidated by several examples,without being limited thereby.

FIGURES

FIG. 1: Flow chart of a process for the manufacture of an acidic proteinformula (12 g/100 ml) based on non-hydrolysed whey protein, according tothe invention (Example 1 and Example 2).

FIG. 2: Particle size distribution of the formulation of Example 1,processed according to the flow chart of FIG. 1, as measured with aMalvern Mastersizer 2000.

-   -   (a): product after homogenization at 30° C. and a pressure of        550/50 bar;    -   (b): product after spray-cooking at 110° C. for approximately 50        ms;    -   (c): product after UHT-pasteurization at 92° C. for 30 sec using        a plate heat exchanger. The product is liquid with a viscosity        of 150 mPa·s at a shear rate of 100 s⁻¹; the product has a        smooth mouth feel.

FIG. 3: Particle size distribution of the formulation of Example 1,processed with a Scraped Surface Heat Exchanger (SSHE), as measured witha Malvern Mastersizer 2000.

-   -   (a): particle size distribution before SSHE processing.    -   (b): particle size distribution after SSHE processing.

FIG. 4: Flow chart of a process for the manufacture of an acidic proteinformula (16 g/100 ml) based on non-hydrolysed whey protein, according tothe invention (Example 3).

FIG. 5: Particle size distribution of the formulation of Example 3,processed according to the flow chart of FIG. 4, as measured with aMalvern Mastersizer 2000.

-   -   (a): product after homogenization at 30° C. and a pressure of        550/50 bar but before spray-cooking;    -   (b): product after spray-cooking at 120° C. for approximately 50        ms;    -   (c): product after UHT-pasteurization at 92° C. for 30 sec using        a plate heat exchanger.    -   (d): product after retort-pasteurization at 92° C. for 30 sec.

FIG. 6: Viscosity of spray-cooked and non spray-cooked samples ofExample 3 when subjected to a temperature/time profile where:

-   -   Curve a) is the temperature/time profile;    -   Curve b) is the viscosity versus time for a non spray-cooked        sample;    -   Curve c) is the viscosity versus time for a spray-cooked sample.        The left Y-axis refers to the viscosity, the right Y-axis to the        temperature. Time is plotted on the x-axis.

FIG. 7: Flow chart of a process for the manufacture of a neutral proteinformula (16 g/100 ml) based on whey protein (Example 4).

EXAMPLES

A number of compositions were manufactured using the method according tothe invention. These are summarized in Table 1.

TABLE 1 Nutritional composition Component A1 A2 A3 A4 A5 Energy value1.6 1.6 2.4 2.4 0.75 (kcal/ml) Protein WPC WPI WPI WPI WPI (g/100 ml) 1212 16 16 12 (En %) 30 30 27 27 58 Fat (g/100 ml) 4.4 4.4 8.5 8.5 0.75(En %) 25 25 31 31 9 Carbohy- drates (g/100 ml) 18 18 25 25 5 (En %) 4545 42 42 27 Dietary fibre 1.2 1.2 0 0 1.2 Vitamins and % of RDI % of RDI% of RDI % of RDI % of RDI Minerals Final pH 4.0 4.0 4.1 7.5 4.0

Example 1 Acidic Whey Protein Composition (12 g/100 ml) (Composition A1)

A flow chart of the process is shown in FIG. 1. The protein (WPC powderof Lactalis, Prolacta 80), carbohydrates and minerals were dispersed inwater and the solution was set to pH 4.0 using 50% lactic acid. The oilwas blended into the product and the pre-emulsion was homogenised at 40°C. in a 2-stage homogenizer at a pressure of 550/50 bar. The product wasthen atomised into the spray-cooking chamber and instantly heated to110° C. by mixing with steam and held at this temperature forapproximately 50 msec. Subsequently, the product was flash-cooled to 50°C. and pumped into a holding tank. The final pH of the product wasadjusted to pH 4.0 and the product was then UHT pasteurized at 92° C.for 30 sec and filled into 200 ml bottles. The product was liquid, witha viscosity of 150 mPa·s at 20° C. at a shear rate of 100 s⁻¹. Theproduct had a smooth mouth feel. This is confirmed by the particle sizedistribution (FIG. 2), which shows that the spray-cooking has littleeffect on the particle size. Moreover, the spray-cooking step appears tohave stabilised the protein aggregates against further aggregation: theparticle size after UHT pasteurization is nearly unchanged compared tothe spray cooked intermediate product. The average particle diameter asobtained from static light scattering (Malvern Mastersizer 2000),d[4,3], after homogenisation (a), spray-cooking (b) and UHTpasteurization (c) were 7.7 μm, 6.0 μm and 5.4 μm, respectively.

Example 2 Acidic Whey Protein Composition (12 g/100 ml) (Composition A2)

A recipe with composition A2 was made according to the process ofExample 1. WPI powder from Fonterra (LGI 895) was used as the proteinsource. The final product was liquid, with a very low viscosity of 15mPa·s at a shear rate of 100 s⁻¹. The product had a smooth mouth feel.The average particle diameter as obtained from static light scattering(Malvern Mastersizer 2000), d[4,3], after UHT pasteurization was 5.7 μm.Composition A5 was made in a similar way as composition A2.

Example 3 Acidic Whey Protein Composition (16 g/100 ml) (Composition A3)

A flow chart of the process is shown in FIG. 4. The protein (WPI)(Bipro®, Davisco), carbohydrates and minerals were dispersed in waterand the solution was set to pH 4.1 using citric acid. The oil wasblended into the product and the pre-emulsion was homogenised at 40° C.in a 2-stage homogenizer at a pressure of 550/50 bar. The product wasthen atomised into the spray-cooking chamber and instantly heated to120° C. by mixing with steam and held at this temperature forapproximately 50 msec. Subsequently, the product was flash-cooled to 50°C. and pumped into a holding tank. The final pH of the product wasadjusted to pH 4.1 and the product was split in two batches. One batchwas then UHT pasteurized at 92° C. for 30 sec and filled asepticallyinto aseptic 200 ml bottles. The product was liquid, with a viscosity of75 mPa·s at a shear rate of 100 s⁻¹. The other batch was retorted (15minutes at 92° C.). This product was liquid with a viscosity of 162mPa·s at a shear rate of 100 s⁻¹ Both products had a smooth mouth feel.This is confirmed by the particle size distribution (FIG. 5), whichshows that the spray-cooking has little effect on the particle size.Moreover, the spray-cooking step appears to have stabilised the proteinaggregates against further aggregation: the particle size after UHT andretort pasteurization is nearly unchanged compared to the spray-cookedintermediate product. The average particle diameter as obtained fromstatic light scattering (Malvern Mastersizer 2000), d[4,3], afterhomogenisation (a), spray-cooking (b) and UHT pasteurization (c) orretorting (d) were 4.7 μm, 3.7 μm, 3.9 μm or 3.8, respectively. It wasobserved that the mineral levels had only small effects on the finalproduct characteristics like particle size, viscosity and shelf lifestability.

In order to illustrate the effect of protein stabilization duringspray-cooking, non spray-cooked and spray-cooked emulsions weresubjected to the same heat treatment in a rheometer. Samples were heatedup to 90° C., kept at 90° for 10 minutes and cooled back while measuringthe viscosity. The temperature versus time curve is given in FIG. 6,curve (a). As can be seen, the non spray-cooked emulsion (b) shows alarge jump in viscosity when the temperature exceeds 80° C., while theviscosity of the spray-cooked emulsion (c) largely stays unaffected,illustrating the stabilizing effect of the method according to theinvention.

Example 4 Neutral Whey Protein Composition (16 g/100 ml) (CompositionA4)

A flow chart of the process is shown in FIG. 7. The whey protein isolate(WPI) (Bipro®, Davisco) and sucrose were dispersed in demineralisedwater and the solution was adjusted to pH 7.5 using a 10% KOH solution.Oil was blended into the product and the pre-emulsion was homogenised at40° C. in a 2-stage homogenizer at a pressure of 550/50 bar. The productwas then atomised into the spray-cooking chamber and instantly heated to170° C. by mixing with steam and held at this temperature forapproximately 100 ms. Subsequently, the product was flash-cooled to 55°C. and aseptically filled into aseptic 200 ml bottles. The product wasliquid, with a viscosity of 97 mPa·s at a shear rate of 100 s⁻¹. Theproduct had a smooth mouth feel. This is confirmed by the particle sizedistribution which shows that the spray-cooking has little effect on theparticle size. If anything, the particles become smaller during theprocess. The average particle diameter as obtained from static lightscattering (Malvern Mastersizer 2000), d[4,3], after homogenisation (a),spray-cooking (b) were 0.48 μm and 0.29 respectively.

Example 5 Comparative Examples

The method according to the invention is compared with several othermethods commonly employed in the field of nutritional compositions usingthe ingredients of composition A1. A summary is given in Table 2.Yoghurt like products with a pH less than pH 4.2 require apasteurization step (either 90° C., 15 min or 92° C., 30 sec) for longshelf life products. The temperature required for pasteurization is wellabove the denaturation temperature of whey proteins. Denatured wheyproteins are reactive molecules capable of aggregate formation. In theexperiments we have observed that the same formulation can form a gel ora liquid product depending on the heating conditions. For example, slowheating in a rheometer, tube heat exchanger, or during gentle mixing inthe retort results in a gelled product. However, when the product isheated under high shear in the surface scraped heat exchanger or heatedinstantaneously to above the denaturation temperature (as in thespray-cooking technique), a liquid products result.

From Table 2, it can be observed that in the case of products that areretort-pasteurized or pasteurized in a tube or plate heat exchanger at atemperature of 80° C. for 30 seconds, large protein aggregates form,leading to gel formation and clogging of the processing equipment. Itwas not possible to process the composition A1, A2 or A3 using thistechnique. We also attempted to process composition A1 using a surfacescraped heat exchanger (SSHE). This technique resulted in a liquidformulation; however the product had an extremely sandy mouth feel,likely due to the formation of large aggregates. This is confirmed bycomparing the particle size distribution of the product (FIG. 3). Theaverage particle size, d[4,3], increases from 7.7 μm (a) to 38 μm (b) asa result of the SSHE processing. However, it is interesting to note thatthe aggregates did not agglomerate to form a gel, suggesting that highshear enabled the formation of inert, but aggregated proteins having alarge and undesirable size.

TABLE 2 Homoge- nization Exp Temp. First heat-treatment PasteurizationRating Remarks Comp. Ex 1 20° C. None retort −− The products gelled 15min at 90° C. during retort sterilization Comp. Ex 2 60° C. Tube orplate heat retort −− Inline gelation of product exchanger 15 min at 90°C. during first heat treatment 30 sec at 80° C. step Comp. Ex 3 30° C.Tube heat exchanger SSHE 0 Liquid product, but very 30 sec at 30° C. 2min at 92° C. sandy Exp E1 40° C. Spray-cooking according to retort +Liquid product with ~400 the invention 50 msec at 15 min at 90° C. mPa ·s, not sandy 110° C. Exp E2 40° C. Spray-cooking according to Plate heatexchanger ++ Very liquid product, with the invention 50 msec at 30 sec92° C. 150 mPa · s, not sandy 110° C. Rating: −−: bad; 0: moderate; +:good; ++: very good

It should be understood that various changes and modifications to thepresently preferred embodiments described herein will be apparent tothose skilled in the art. Such changes and modifications may be madewithout departing from the spirit and scope of the invention and withoutdiminishing its advantages. It is therefore intended that such changesand modifications are covered by the appended claims.

1-26. (canceled)
 27. A liquid enteral nutritional composition,comprising: i) 9 to 20 g of non-hydrolysed globular protein per 100 mlof the composition having a pH>3 and ≦8; ii) 10 to 20 g ofnon-hydrolysed globular protein per 100 ml of the composition; or iii) 9to 20 g of non-hydrolysed globular protein per 100 ml of thecomposition, with the proviso that a UHT-sterilized compositioncomprising 9.2 weight % whey protein having a pH=3 is excluded.
 28. Theliquid enteral nutritional composition according to claim 27, whereinthe composition is sterilized or pasteurized.
 29. The liquid enteralnutritional composition according to claim 27, wherein the globularprotein is selected from the group consisting of whey protein, peaprotein, soy protein, and any mixture thereof.
 30. The liquid enteralnutritional composition according to claim 29, wherein the whey proteinis selected from the group consisting of β-lactoglobulin, α-lactalbumin,serum albumin, or any mixture thereof.
 31. The liquid enteralnutritional composition according to claim 30, wherein the whey proteinis sourced from whey protein concentrate (WPC), whey protein isolate(WPI), or any mixture thereof.
 32. The liquid enteral nutritionalcomposition according to claim 27, wherein the pH is about 2 to
 8. 33.The liquid enteral nutritional composition according to claim 32,wherein the pH is about 4 to
 7. 34. The liquid enteral nutritionalcomposition according to any claim 27, wherein the composition has anenergy density of at least 1.5 kcal/ml.
 35. The liquid enteralnutritional composition according to claim 27, wherein at least 85weight % of the total protein is non-hydrolysed globular protein. 36.The liquid enteral nutritional composition according to claim 27,further comprising a non-globular protein.
 37. The liquid enteralnutritional composition according to claim 36, wherein the non-globularprotein is selected from the group consisting of casein, caseinate,micellar casein isolate, and any mixture thereof.
 38. The liquid enteralnutritional composition according to claim 27, further comprising fat inan amount between 20 to 40% of the total energy content of thecomposition.
 39. The liquid enteral nutritional composition according toclaim 27, wherein the fat comprises long chain triglycerides.
 40. Theliquid enteral nutritional composition according to claim 27, furthercomprising carbohydrate in an amount between 30 to 60% of the totalenergy content of the composition.
 41. The liquid enteral nutritionalcomposition according to claim 40, wherein the carbohydrate comprisesmaltodextrose with a DE of >30.
 42. The liquid enteral nutritionalcomposition according to claim 41, wherein the carbohydrate comprisesmaltodextrose with a DE of about
 47. 43. The liquid enteral nutritionalcomposition according to claim 40, wherein the carbohydrate includesmaltodextrose with a DE of 2 to 10
 44. The liquid enteral nutritionalcomposition according to claim 43, wherein the carbohydrate comprisesmaltodextrose with a DE of about
 2. 45. The liquid enteral nutritionalcomposition according to claim 40, wherein the carbohydrate comprisestrehalose.
 46. The liquid enteral nutritional composition according toclaim 27, wherein the composition has a viscosity lower than 500 mPa·s,measured at 20° C. at a shear rate of 100 s⁻¹.
 47. A liquid enteralnutritional composition according to claim 27 comprising: a) protein,comprising about 12 g of non-hydrolysed whey per 100 ml of thecomposition, the protein providing about 30% of the total energy contentof the composition; b) fat, providing about 25% of the total energycontent of the composition; c) carbohydrate, providing about 45% of thetotal energy content of the composition, wherein the composition havingan energy density of about 1.6 kcal/ml.
 48. A liquid enteral nutritionalcomposition according to claim 27, comprising: a) protein, comprisingabout 16 g of non-hydrolysed whey per 100 ml of the composition, theprotein providing about 27% of the total energy content of thecomposition; b) fat, providing about 31% of the total energy content ofthe composition; c) carbohydrate, providing about 42% of the totalenergy content of the composition, wherein the composition having anenergy density of about 2.4 kcal/ml.
 49. A method of providing nutritionto a person in need thereof, comprising administering to the person thecomposition according to claim
 27. 50. The method according to claim 49,wherein the person is an elderly person, a person that is in a diseasestate, a person that is recovering from a disease state, a person thatis malnourished, a sportsman, or an active elderly.
 51. A method for thepreparation of a liquid enteral nutritional composition, comprising: a)adjusting the pH of an aqueous composition comprising non-hydrolysedglobular proteins to a value of between about 2 and 8; b) converting thecomposition of non-hydrolysed globular proteins obtained in step a) intoan aerosol; c) subjecting the aerosol obtained in step b) to atemperature of 100 to 190° C. for about 30 to 300 milliseconds; d)flash-cooling the heat-treated aerosol obtained in step c) to atemperature below 85° C. to obtain an aqueous solution comprisingheat-treated globular proteins; and optionally, e) sterilizing and/orpasteurizing the solution obtained in step d).
 52. The method accordingto claim 51, wherein at least 85 weight % of the non-hydrolysed globularproteins is whey protein.